21st century medicine

GENETIC MARKERS
Genomes provide insight into the mutations responsible for some diseases, making it possible to develop personalised treatments for them.

Leading pharmaceutical companies: Roche (Switzerland), Novartis (Switzerland), AstraZeneca (UK), AbbVie (US), Biogen (US)

The advent of low-cost genome sequencing has revolutionised the pharmaceutical industry, making it possible to better understand the genetic basis for diseases and to develop targeted treatments. Didier Trono, head of EPFL’s Laboratory of Virology and Genetics (fondly referred to as “Tronolab”), says, “we can now identify the mutations that make you genetically predisposed to some diseases, such as the BRCA1 and BRCA2 mutations that increase the risk of breast and ovarian cancer, or mutations in the low density lipoprotein receptor (LDLR) gene related to hereditary high cholesterol.”

Drugs that repress these mutations are nothing new. Glivec by Novartis is a perfect example. According to Trono, “this drug inhibits a mutation-based enzyme that causes certain forms of leukaemia.” Genome sequencing also enables doctors to examine the genetic profile of each tumour and to tailor treatment specifically to the patient by giving them the most efficient combination of drugs possible. “This is less about developing new drugs and more about better using the ones available.”

As for the pharmaceutical industry, this trend could reduce the number of drugs on pharmacy shelves since every prescription would be fully personalised in the future. But this also opens the way for innovation in diagnostics, specifically for developing genetic testing to put on the market. “Roche is way ahead of the game in this area,” Trono confirms. The Basel-based group teamed up with the British government to sequence 100,000 genomes in cancer patients and people with rare diseases, and has established a partnership with the American company 23and- Me in order to access their genetic data on people with Parkinson’s and Crohn’s disease. These projects should provide Roche with what it needs to develop treatments aimed at the genetic mutations behind these diseases.

IMMUNOTHERAPY - THEACHING THE BODY TO DEFEND ITSELF
This revolutionary method teaches the immune system to target cancer cells or the AIDS virus, and may usher in a new era for treatment.

Leading companies: Roche (Switzerland), AstraZeneca (UK), Bristol-Myers Squibb (US), Merck (US), Novartis (Switzerland)

Immunotherapy uses the patient’s immune system to fight some diseases such as cancer. “This procedure involves infusing patients with T lymphocytes, or T cells, that come from their own body and have been modified by genome editing,” explains Fyodor Urnov, a geneticist at the University of California at Berkeley who helped develop this form of therapy. In 2014, American researchers successfully cured leukaemia patients and injected a T cell mutation that made HIV-positive patients resistant to the AIDS virus.

Roche is currently the no. 1 company in the world for immunotherapy, devoting “over 50% of its R&D budget” to this field according to Bruno Bulic, an analyst at Baader Bank. Roche also developed the first immunotherapy to hit the market – Tecentriq, a drug for lung and bladder cancer patients – and which was FDA-approved in 2016. “AstraZeneca, Bristol-Myers Squibb, Merck and Novartis are also highly invested in this area,” says Bulic.

The next phase will focus on the genome-editing tool CRISPR-Cas9, which was discovered in 2012. “With this technique you can insert, delete or reorder bits of genetic code, which can promote or inhibit genes,” says Martin Jinek, a biochemist at the University of Zurich, who worked in the American lab that discovered it. “The primary advantage is that it’s fast and extremely precise.” The first clinical trial using immunotherapy and CRISPR- Cas9 is set to take place in China this autumn for lung cancer patients.

LIVING DRUGS
Made with the patient’s own blood and cells, these drugs have made substantial progress, making them significantly more profitable.

Leading companies: Genentech (Roche Group – Switzerland), Sandoz (Novartis – Switzerland), Amgen (US), Biogen (US), Johnson & Johnson (US)

The first biodrugs – made from living components like blood plasma and proteins – came out in the 1980s. Up until recently they were used to treat inflammatory diseases such as rheumatoid arthritis and Crohn’s disease (chronic inflammation in the digestive system), but according to Graham Jones, a biodrug specialist at Tufts University, “the latest developments have been in oncology.” Genentech, an American group which Roche acquired in 2009, has been a trailblazer for biodrugs. “In 1998, Genentech put the revolutionary drug Herceptin on the market, dramatically increasing life expectancy for people suffering from breast cancer,” says Bruno Bulic at Baader Bank. Then from 2009–2013, a series of drugs for skin cancer, leukaemia and breast cancer followed.

Significant developments have also been made to improve the production process. The production of biodrugs is labour-intensive and costly because they are made from living components,” Jones adds. “But in recent years, pharma companies have managed to improve the yield and the purity of these substances.”

Biosimilar drugs, which are generic versions of biodrugs, have also undergone substantial improvements despite the initial hesitation to delve into such a complicated process. Jones asserts that “the proteins that are the basis for biodrugs are unstable and unpredictable, so it’s really difficult to copy them to the letter.” In 2015, however, Sandoz – a Novartis subsidiary – became the first group to do it. Sandoz released a biosimilar called Zarxio, a legitimate copy of the Amgen drug used to treat leukaemia. Last June, European authorities approved Rixathon, the Swiss company’s biosimilar for Rituximab, which is used to treat blood cancers and certain auto-immune diseases.

RARE AND LIFE-THREATENING DISEASES TAKE THE SPOTLIGHT
Interest in rare diseases has been picking up in recent years. Now that the approval process can be streamlined, it’s much easier to release drugs on the market to treat them.

Leading companies: Pfizer (US), Baxter (US), Bayer (Germany), Bristol-Myers Squibb (US), Novo Nordisk (Denmark), Santhera (Switzerland)

Pharma companies now have renewed interest in rare diseases that have long been on the back burner. Graham Jones from Tufts University asserts that “with the FDA Fast Track approval process for drugs [used to treat serious or life-threatening conditions], companies are encouraged to invest in this area.” One such drug to benefit from accelerated approval was Ivacaftor, developed by the US-based company Vertex, which targets 4% of people suffering from cystic fibrosis – that’s 1,200 Americans.

The Swiss company Santhera came up with a unique approach. “Instead of looking for new drugs, it tests pre-existing drugs to see if they have an effect on rare or life-threatening diseases,” says Bob Pooler, an analyst at ValuationLAB, which evaluates the company for investors. That’s how they discovered that Idebenone – a drug developed by Takeda Pharmaceutical Company in Japan for Alzheimer’s – was extremely efficient in treating Leber’s hereditary optic neuropathy (LHON), an eye disorder that affects one in a million people. The drug was approved in Europe for this new purpose in 2015.

“Now Santhera wants to get it approved for Duchenne muscular dystrophy (DMD),” claims Pooler. “We are expecting the request to go through in Q3 of this year.” This would make the number of patients taking Idebenone skyrocket. “The drug can also treat one form of multiple sclerosis present in 15% of those afflicted,” he says. If it were approved for treating this disease, the number of patients taking it would be even higher.

THE WAR AGAINST SUPER BACTERIA
Drug-resistant bacteria has become a serious public health issue. Much to the delight of pharma companies, many countries have set up funds to promote research for new antibiotics.

Leading companies: GlaxoSmith- Kline (UK), Roche (Switzerland), AstraZeneca (UK), The Medicines Company (US), Basilea (Switzerland)

From 1960 to 1980, the quantity of new antibiotics on the market increased exponentially. But then came a wave of chronic underinvestment as pharmaceutical companies realised that the most straightforward discoveries in pharmaceuticals had already been made. On top of that, with little return on investment, El Dorado was unattainable for antibiotics. Patients only generally take them in the shortterm, roughly one to six weeks, and they are inexpensive. High blood pressure or diabetes medication, however, is a lifetime investment.

But in 2010 when drug-resistant bacteria became a serious public health threat, a slew of initiatives were launched in the hope of spurring research for new antibiotics. The EU invested hundreds of millions of euros in the Innovative Medicines Initiative (IMI) and the US government agency called the Biomedical Advanced Research and Development Authority (BARDA). A number of pharmaceutical companies benefitted from the influx of funding.

Takeovers such as Merck’s acquisition of the American startup Cubist Pharmaceuticals and Pfizer’s purchase of the antibiotics division at AstraZeneca have also ramped up antibiotic research. In Switzerland, the industry is headed by the giants Basilea, Novartis and Debiopharm. Basilea released a fifth-generation cephalosporin – an antibiotic – known as Ceftobiprole in Europe and Canada, and received $100 million from BARDA to get it approved in the US.